Hearing loss is a key risk factor for dementia [1]. In this scenario, fluid exchange between the cochlea and brain remains an unexplored mechanism and therapeutic target, partly due to inaccessibility of the cochlear anatomy. Existing in vitro models lack biomimetic fidelity to replicate its native features.
[1] Livingston, G et al. The Lancet. 2020.
THE GOAL of EAR2BRAIN is to develop develop a patient-specific 3D biomimetic platform that mimics cochlear anatomy and fluid dynamics, coupling in silico, in vitro and advanced medical imaging approaches, to study sound pressure and molecular exchange between the inner ear and brain, with the ambitious goal of opening new paths for dementia prevention.
Multiphysics Modeling of Inner Ear Fluid Dynamics
The project begins with advanced finite element analysis of three-dimensional geometries representing the inner ear and its interface with surrounding tissues. Multiphysics simulations combine fluid dynamics, mechanical behavior, and molecular transport to investigate how sound-induced forces interact with cochlear and labyrinthine fluids.
These models are used to explore pressure distributions across different compartments of the inner ear and at the interface with the meninges, under both physiological and pathological conditions. For the first time, this approach enables a comprehensive analysis of acoustofluidic phenomena and the associated molecular exchanges, offering new insights into how mechanical vibrations and fluid transport are coupled within the auditory system.
Biofabrication of a 3D Biomimetic, MRI-Compatible Cochlear Model
At the core of the project is the development of an innovative lab-on-a-chip device that recreates the interface between the inner ear and the brain. This miniaturized platform enables the study of complex biological processes, such as protein accumulation associated with neurodegeneration, within a controlled and highly engineered environment.
To achieve this goal, advanced 3D fabrication and biofabrication techniques are employed to generate biomimetic, three-dimensional structures that can be perfused with fluids. This approach allows precise control of intracochlear and intracranial pressure conditions, providing a realistic and versatile model for investigating fluid dynamics and ear–brain interactions.
Visualizing hidden fluid exchanges
High-resolution preclinical MRI enables non-invasive visualization and quantitative analysis of fluid distribution and dynamics within complex biological systems. Applied to in vitro models, it allows the tracking of fluid pathways, the measurement of subtle pressure-related changes, and the detection of micro-scale variations in fluid composition and movement. This level of imaging makes it possible to observe otherwise invisible exchanges between compartments, providing detailed spatial and temporal information on fluid behavior without disrupting the system.